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PubMed1993

Studies of herpesvirus infection in chronic fatigue syndrome.

The relationship of herpesviruses to chronic fatigue syndrome has received considerable attention over the past decade. Data suggesting an association fall into three major categories. First, among acute precipitants of the syndrome are primary infections with some herpesviruses, most notably Epstein-Barr virus and cytomegalovirus. Second, a series of studies have detailed elevations of antibodies to most herpesviruses in selected chronic fatigue syndrome populations, with Epstein-Barr virus and human herpes type 6 being the objects of most scrutiny. Third, one recent study reported a greater ease of recovery of human herpes virus type 6 from chronic fatigue syndrome patients. This review article critically examines the cumulative data regarding an association between one or more herpesviruses and the chronic fatigue syndrome in the context of the known biology and epidemiology of these agents. In view of these, and additional considerations regarding study methodologies, the conclusion is drawn that herpesviruses are not dominant causes of the chronic fatigue syndrome and may not even be necessary to the perpetuation of the illness, but it is premature to dismiss entirely this latter possibility.

Cytomegalovirus↗

PubMed2002

Detection of herpesvirus infection of the CNS: the experience of hospital Geral de Santo António.

BACKGROUND: PCR detection of CSF Herpes virus DNA is an important tool in the diagnosis of CNS infections. Use of this test has been shown to have an impact on patient management as measured by shortened patient stays, specific therapeutic intervention, reduction of empirical expensive therapy administration, all of which should translate into significant health care savings. OBJECTIVE: The present study aimed at implementing, and evaluating both clinically and analytically the performance of several commercially available PCR based assays for the detection of Herpes virus infections of the CNS. STUDY DESIGN: A total of 314 patients with suspected CNS Herpesvirus infection were investigated, between 1999 and 2001, by Stair primers PCR. Starting on January 2002, two commercially available real-time-PCR systems were implemented and tested using the Stair primers PCR assay as golden standard and three external control proficiency panels along with serial dilutions of positive clinical samples. RESULTS: Sensitivity of the assay was determined to be <200 copies per ml for HSV and <1250 copies per ml for CMV. Positive results were obtained for 17 patients (6 HSV-1, 1 HSV-2, 1 EBV, 1 CMV, 6 VZV and 2 HHV-6) whose clinical and analytical findings were consistent with the PCR results. A real-time-PCR procedure was introduced in 2002 with similar sensitivity, but a more rapid response. CONCLUSION: Conventional end-point PCR proved useful to the diagnosis of CNS herpes virus infection, with an impact on the clinical intervention. However, the use of Real-Time-PCR has greatly enhanced these advantages, making results available at a much earlier time, thus significantly reducing the need for empirical treatment.

Central Nervous System Viral Diseases↗

PubMedDate not supplied

Herpesvirus infection of the respiratory tract electronmicroscopic observation of the virus in cells obtained from a sputum cytology.

A case of herpesvirus infection of the respiratory tract in which the virus was seen ultrastructurally in cells obtained from a routine sputum collected for cytology studies, is presented. The method described would seem feasible for additonal studies at the ultrastructural level of cells obtained during collection of material for routine cytology of the respiratory tract. In the present case the virus particles were easily seen and characterized.

Cell Nucleus↗

PubMed1993

Future management of herpesvirus infections.

The clinical investigations conducted to date with herpesviruses have provided a good grounding into the general principles of herpesvirus replication and pathogenesis. Multiple opportunities for intervention include prevention of initial infection, prevention of reactivation, suppression of reactivated virus, and treatment of established disease. Studies have shown that each of these approaches can be effective against one or more herpesviruses. What is needed now are studies combining sequential interventions so that patients who fail, for example, prophylaxis with one drug can be entered directly into trials of suppression and then into pre-emptive therapy, each with different antiviral agents. In this way, it is to be hoped that increasing proportions of cohorts of susceptible patients will suffer less from herpesvirus infections. Clearly, the design of such clinical trials needs to be constantly refined as methods of diagnosis and understanding of pathogenic mechanisms improve and as new agents are discovered.

Antiviral Agents↗

PubMedDate not supplied

[Treatment of experimental herpesvirus infection with nonsteroidal anti-inflammatory agents].

The therapeutic effect of nonsteroid antiinflammatory drugs (pyrazolone and salicylate derivatives) and their combinations with acyclovir was assessed in experimental herpesvirus infection in cell culture and in mice. A combination of 4-iodoantipyrine and acyclovir protected mice from herpesvirus encephalitis. This effect was associated with a decrease of the level of the virus in mouse brain and an increase of the titers of serum interferon and virus neutralizing antibodies.

Acyclovir↗

PubMed1986

Effect of herpesvirus infections on T-lymphocyte subpopulations and blastogenic responses in renal transplant recipients receiving cyclosporine.

The immunosuppressive effects of three herpesviruses--cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV)--were assessed in 29 renal transplant recipients treated with cyclosporine and prednisone. The ratios of Leu 3-positive ("helper-inducer") to Leu 2-positive ("suppressor-cytotoxic") T lymphocytes in peripheral blood were only moderately and transiently decreased during primary CMV infection, with or without concurrent reactivated EBV and HSV infections. This effect was due to an increase in absolute numbers of Leu 2-phenotypic and decrease in Leu 3-phenotypic T cells and was associated with symptomatic viral illness. Reactivated CMV infection alone or together with reactivated EBV and HSV infections resulted in less significant alterations in T-cell subsets than did primary CMV infection. Lymphocyte blastogenesis was not significantly altered during the herpesvirus infections. The data suggest that cyclosporine treatment inhibits the activation of suppressor cells and depression of cellular immune function that have been associated with herpesvirus infections in renal transplant recipients undergoing conventional immunotherapy.

Adolescent↗

PubMed1995

Rapid detection and distinction of cutaneous herpesvirus infections by direct immunofluorescence.

BACKGROUND: Optimal management of cutaneous herpes simplex virus (HSV) and varicellazoster virus (VZV) infections requires rapid, accurate distinction between these pathogens. OBJECTIVE: In a mixed-case series of suspected cutaneous herpesvirus infections, we compared the diagnostic utility of viral culture and direct immunofluorescence (DIF) using a panel of fluoresceinated monoclonal antibodies against HSV and VZV. METHODS: Epifluorescence microscopy of smears and viral culture were performed in parallel on 58 lesions. RESULTS: DIF and culture were equally sensitive (88%) in HSV infections, whereas DIF was four times as sensitive as culture (100% vs 18%) in VZV. DIF either refuted an incorrect clinical diagnosis or permitted definitive laboratory diagnosis of a clinically indeterminate lesion in 7 (12%) of 58 lesions tested. CONCLUSION: DIF is a rapid, simple, sensitive, specific, cost-effective, and clinically useful technique for detecting and distinguishing cutaneous HSV and VZV infections.

Antibodies, Monoclonal↗

PubMed1998

3-Hydroxyphthaloyl beta-lactoglobulin. IV Antiviral activity in the mouse model of genital herpesvirus infection.

The spread of sexually transmitted infections caused by herpes simplex virus type 2 (HSV-2) has continued unabated despite educational efforts generated in response to the human immunodeficiency virus (HIV) epidemic. Given the absence of effective vaccines, this indicates the need to develop prophylactic measures such as topical antiviral agents. Chemical modification of bovine beta-lactoglobulin (beta-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the generation of a potent HIV-1 inhibitor designated 3HP-beta-LG. This agent was shown to also have antiviral activity against HSV-2 and HSV-1 in vitro. Recent studies indicate that 3HP-beta-LG binds to HSV-1 virions, which, at least in part, involves the viral glycoprotein gE. Here we show that 3HP-beta-LG inhibits HSV-2 infection in the mouse model of genital HSV-2 infection. Simultaneous exposure to HSV-2 and 3HP-beta-LG caused a significant decrease in the proportion of infected animals (27% virus shedding, 5% lesion development and 0% fatality for 3HP-beta-LG as compared to 80% shedding, 60% lesion development and 53% fatality in mice treated with PBS). The proportion of animals with HSV-2 infection after treatment with beta-LG was similar to that in the PBS-treated group. Pretreatment with 3HP-beta-LG formulated in a gel, which prolongs the presence of the agent in the vagina, also significantly reduced the proportion of HSV-2-infected mice (5% virus shedding, 5% lesion development and 0% fatality for 3HP-beta-LG as compared to 70% shedding, 60% lesion development and 40% fatality in vehicle-treated mice). These differences were significant (P < or = 0.0005, 0.002 and 0.008 for shedding, lesion development and fatality, respectively). Virus titres in the minority of mice that developed infection were similar to those in untreated mice. HSV-2 infection was not inhibited by treatment of an ongoing infection, indicating that 3HP-beta-LG interferes with the initial infection. These data suggest that 3HP-beta-LG may be an efficacious agent for preventing vaginal transmission of genital herpesvirus infections.

Animals↗

PubMed2002

Enhanced atherogenesis is not an obligatory response to systemic herpesvirus infection in the apoE-deficient mouse: comparison of murine gamma-herpesvirus-68 and herpes simplex virus-1.

Viral and bacterial infectious agents have been implicated in the etiology of atherosclerosis. We have previously shown that a gamma-herpesvirus can accelerate atherosclerosis in the apolipoprotein E-deficient (apoE-/-) mouse. To address whether a virally induced systemic immune response is sufficient to trigger enhanced atheroma formation, we infected apoE-/- mice with murine gamma-herpesvirus-68 (MHV-68) or herpes simplex virus-1 (HSV-1). In this study, we show that both viruses were able to induce a cell-mediated and humoral immune response in the apoE-/- mouse, which was sustained over a period of 24 weeks. Although intranasal or intraperitoneal infection with MHV-68 induced similar levels of virus-specific IgG1 and IgG2a antibodies in the serum of apoE-/- mice, those infected with HSV-1 showed higher anti-HSV-1 IgG2a compared with IgG1 antibody levels. In addition, viral message was not detected in the aortas of HSV-1-infected animals, whereas we have shown previously that MHV-68 mRNA can be detected in the aortas of infected mice as early as 5 days after infection. Compared with control mice, apoE-/- mice infected with MHV-68 showed accelerated atherosclerosis, whereas mice infected with HSV-1 did not. These data indicate that a systemic immune response to any particular infectious agent is insufficient to induce enhanced atherosclerosis in the apoE-/- mouse and point to specific infections or immune mechanisms that might be essential for virally enhanced atherogenesis.

Animals↗

PubMed1991

[Human herpesviruses infections (I)--EBV infection and immunity in cancer patients].

Human herpesviruses have been known to be reactivated from latent infection iin immunosuppressed individuals. To assess the immunity, antibodies to human herpesviruses (VZV, HSV, CMV and EBV) were measured in patients with gastrointestinal cancer and normal persons ranging from 40 to 80 in age. CF antibodies to herpesviruses except for EBV were negative in normal persons below the age of 60 and cancer patients aged 60 and over. The CF antibody titer higher than 1:64 occurred only in young cancer patients and older normal persons. The titer of VCA antibody to EBV ranged from 1:40 to 1:160 in more than 80% of normal persons and was higher than 1:640 in less than 7%. The ratio those with antibody negative or below 1:40 increased with the age. In contrast, the titer was higher than 1:320 in 70% of the patients, and the antibody was negative in none of them. In addition, the low titer occurred only in less than 5%. The rate of patients having higher VCA antibody titers increased with age, and the titer was high in more than 50% of patients in the 8th decade. In cancer patients, the higher the VCA antibody titer was, the less number of mature B cells, target cells of EBV, and the B cell functions were observed. This suggests that reactivation of EBV in hosts bearing carcinomas results in a fall of production of the specific antibody.

Adult↗

PubMed2005

A common genetic variant in FCGR3A-V158F and risk of Kaposi sarcoma herpesvirus infection and classic Kaposi sarcoma.

Associations of FCGR3A among men with HIV/acquired immunodeficiency syndrome suggest that host responses affect the pathogenesis of Kaposi sarcoma herpesvirus (KSHV) infection and risk of acquired immunodeficiency syndrome-associated Kaposi sarcoma. Using DNA from two HIV seronegative case-control populations in Italy, we examined whether the functional FCGR3A-V158F variant was associated with risk of KSHV infection or classic Kaposi sarcoma (CKS). In population I, we examined FCGR3A variants and risk of KSHV infection in 34 KSHV latent nuclear antigen (LANA)-seropositive and 120 LANA-seronegative adults from Sardinia (52% male; median age, 45 years; range, 31-60), whereas in population II, we examined risk of CKS from 133 CKS cases and 172 KSHV LANA-seropositive controls from Sicily, Rome, and Naples (70% males; median age, 74 years; range, 29-91). FCGR3A variants were determined by direct sequence analysis of a nested PCR of genomic DNA assay using allele-specific primers. KSHV LANA was determined by immunofluorescence assay. Overall, compared with the 158F allele, 158V was overrepresented among controls from both Mediterranean populations (frequency = 0.52 and 0.51, respectively). After controlling for age, 158V homozygous women were at increased risk of KSHV infection and CKS compared with 158F homozygous women [odds ratio (OR), 8.7; 95% confidence interval (95% CI), 0.8-98 and OR, 3.8; 95% CI, 1.0-14, respectively], whereas homozygous men were at decreased risk (OR, 0.4; 95% CI, 0.1-2.3 and OR, 0.4; 95% CI, 0.2-0.8, respectively). Significant gene-dose effects were observed among men and women at risk for CKS (P(trend) < or = 0.05). Our findings suggest that gender differences could possibly modify the effect of FCGR3A on risk of KSHV infection and CKS. Additional studies are required to confirm these relationships and determine their etiologic significance.

Adult↗

PubMed1985

Biotransformation and elimination of [2-14C]-1-(2-deoxy-2'-fluoro-beta-D -arabinofuranosyl)-5-iodocytosine in immunosuppressed patients with herpesvirus infections.

The metabolism of the drug [2-14C]-1-(2'-deoxy-2'-fluoro-beta-D -arabinofuranosyl)-5-iodocytosine (FIAC), a potent inhibitor of herpesvirus replication, was studied in immunosuppressed patients with herpesvirus infections. FIAC was administered intravenously by 15-min infusion and by mouth 24 h later to four patients at doses of 50 or 100 mg/m2. FIAC was cleared from the plasma primarily by biotransformation in liver, kidney, and peripheral blood, with a terminal-phase half-life of 0.92 to 1.80 h (mean, 1.36 h) after intravenous administration. The area under the concentration-time curve from zero to infinity (AUC0-infinity) for FIAC was 1.6 to 4.7% (mean, 3.4%) of the AUC0-infinity for total radioactivity. 1-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) was the major metabolite; the AUC0-infinity for FIAU was 54.3 to 72.5% (mean, 63.4%) of the AUC0-infinity for total radioactivity. The terminal-phase half-life for FIAU was 3.32 to 4.49 h (mean, 3.91 h); FIAU was cleared from plasma by renal elimination and further biotransformation. lesser amounts of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine, the glucuronide conjugates of these metabolites, and the glucuronide conjugates of FIAC and FIAU were also formed. A comparison of the AUC0-infinity for total radioactivity after intravenous and oral administration suggested that nearly all of the oral dose was absorbed. Plasma levels of FIAU, also a potent inhibitor of herpesvirus replication in vitro, exceeded the 50% effective dose for herpes simplex virus and varicella-zoster virus as late as 12 h after administration of FIAC.

Adult↗

PubMed1992

Epizootiological aspects of type 1 and type 4 equine herpesvirus infections among horse populations.

The dissemination of equine herpesvirus types 1 (EHV-1) and 4 (EHV-4) among various horse populations in Japan was investigated through the isolation and typing of virus strains from horses with respiratory diseases. Type specific monoclonal antibody pools were used for the typing of isolates. The 42 strains of EHV-1 and 64 strains of EHV-4 were isolated from 4593 nasal swabs and/or blood plasma samples collected from 3326 horses during a period from 1979 to 1990. All the strains of EHV-1 were isolated from racehorses only and during the winter season exclusively, when the epizootic of respiratory diseases occurred among racehorse populations at two Training Centers of the Japan Racing Association. In contrast, the strains of EHV-4 were isolated from horses irrespective of the season, facility, or horse population; foals and yearlings in breeding farms and our institute, rearing horses in rearing farms, and racehorses. Especially, 4 strains of EHV-4 were isolated from plasma samples containing buffy coat cells. We believe this is the first reported case of EHV-4 cell-associated viremia in the world. All 87 strains isolated from aborted fetuses were identified as EHV-1. The results suggest that EHV-1 is responsible for epizootic respiratory diseases in racehorses in the winter and abortion among mares at the late stage of gestation, and that EHV-4 causes respiratory diseases throughout the year among all horse populations.

Abortion, Veterinary↗

PubMed2005

Constitutively active K-cyclin/cdk6 kinase in Kaposi sarcoma-associated herpesvirus-infected cells.

BACKGROUND: Kaposi sarcoma-associated human herpesvirus (KSHV) encodes K-cyclin, a homologue of D-type cellular cyclins, which binds cyclin-dependent kinases to phosphorylate various substrates. K-cyclin/cdk phosphorylates a subset of substrates normally targeted by cyclins D, E, and A. We used cells naturally infected with KSHV to further characterize the biochemical features of K-cyclin. METHODS: We used immunoprecipitation with K-cyclin antibodies to examine the association of K-cyclin with cdk2, cdk6, p21Cip1, and p27Kip1 proteins in BC3 cells. We separated populations of BC3 cells enriched in cells in G1, S, or G2/M phases by elutriation and measured K-cyclin protein and the kinase activity of K-cyclin/cdk6 complexes. The half-life of K-cyclin and cyclin D2 proteins was determined by blocking protein synthesis with cycloheximide and measuring proteins in cell lysates by western blot analysis. We fused the entire K-cyclin sequence to the carboxyl-terminal sequence of cellular cyclin D that contains the PEST degradation sequence to produce K-cyclin/D2 and transfected K-cyclin/D2 into K-cyclin-negative cells to investigate the effect of the PEST sequence on K-cyclin's stability. RESULTS: Viral K-cyclin interacted with cyclin-dependent kinases cdk2, cdk4, and cdk6 and with the cyclin/cdk inhibitory proteins p21Cip1 and p27Kip1 in BC3 cell lysates. Unlike D-type cyclins, whose expression is cell cycle dependent, the level of K-cyclin was stable throughout the cell cycle, and the kinase associated with the K-cyclin/cdk6 complex was constitutively active. The half-life of K-cyclin (6.9 hours) was much longer than that of cellular cyclin D2 (0.6 hour) and that of K-cyclin/D2 (0.5 hour), probably because K-cyclin lacks the PEST degradation sequence present in D-type cyclins. CONCLUSION: The constitutive activation of K-cyclin/cdk complexes in KSHV-infected cells appears to result from the extended half-life of K-cyclin and may explain its role in Kaposi sarcoma.

Blotting, Western↗

PubMed2002

Prevalence of Kaposi sarcoma-associated herpesvirus infection in homosexual men at beginning of and during the HIV epidemic.

CONTEXT: Some studies have inferred that an epidemic of Kaposi sarcoma-associated herpesvirus (KSHV) infection in homosexual men in the United States occurred concurrently with that of human immunodeficiency virus (HIV), but there have been no direct measurements of KSHV prevalence at the beginning of the HIV epidemic. OBJECTIVES: To determine the prevalence of KSHV infection in homosexual men in San Francisco, Calif, at the beginning of the HIV epidemic in 1978 and 1979 and to examine changes in prevalence of KSHV at time points from 1978 through 1996 in light of changes in sexual behavior. DESIGN, SETTING, AND PARTICIPANTS: Analysis of a clinic-based sample (n = 398) derived from the San Francisco City Clinic Cohort (ages 18-66 years) (n = 2666 for analyses herein) and from population-based samples from the San Francisco Men's Health Study (MHS) (ages 25-54 years) (n = 825 and 252) and the San Francisco Young Men's Health Study (YMHS) (ages 18-29 years) (n = 428-976, and 557); behavioral studies were longitudinal and KSHV prevalence studies were cross-sectional. MAIN OUTCOME MEASURES: Antibodies against KSHV and HIV; sexual behaviors. RESULTS: The prevalence of KSHV infection in 1978 and 1979 was 26.5% of 235 (a random sample) overall (weighted for HIV infection) vs 6.9% (128/1842) for HIV in the San Francisco City Clinic Cohort sample. The prevalence of KSHV infection remained essentially unchanged between an MHS sample of 252 in 1984 and 1985 (29.6%) and a YMHS sample of 557 in 1995 and 1996 (26.4%), while HIV prevalence dropped from 49.5% of 825 in 1984 and 1985 (MHS) to 17.6% of 428 in 1992 and 1993 (YMHS). The proportion of men practicing unprotected receptive anal intercourse with 1 or more partners declined from 54% to 11% during the 1984 through 1993 period (MHS) with similar though slightly higher values in the YMHS in 1992 and 1993; whereas for unprotected oral intercourse it ranged between 60% and 90% in the 1984 through 1996 period (MHS and YMHS). CONCLUSIONS: Infection with KSHV was already highly prevalent in homosexual men when the HIV epidemic began in San Francisco, and its prevalence has been maintained at a nearly constant level. Any declines in the incidence of Kaposi sarcoma do not appear to be caused by a decline in KSHV transmission.

Adult↗

PubMed2004

Comparison of nested PCR and real time PCR of Herpesvirus infections of central nervous system in HIV patients.

BACKGROUND: Molecular detection of herpesviruses DNA is considered as the reference standard assay for diagnosis of central nervous system infections. In this study nested PCR and real time PCR techniques for detection of Herpes simplex virus type 1 (HSV-1), Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in cerebrospinal fluid of HIV patients were compared. METHODS: Forty-six, 85 and 145 samples previously resulted positive for HSV-1, CMV and EBV by nested PCR and 150 randomly chosen negative samples among 1181 collected in the period 1996-2003 were retrospectively reassessed in duplicate by real time PCR and nested PCR. RESULTS: Samples giving positive results for CMV, HSV-1 and EBV with nested PCR were positive also with real time PCR. One of the negative samples resulted positive for HSV and one for EBV. Real time PCR showed comparable sensitivity and specificity vs nested PCR. CONCLUSION: Real time PCR proved to be a suitable method for diagnosis of herpesvirus infections in CNS, showing comparable sensitivity and being less time consuming than nested PCR.

AIDS-Related Opportunistic Infections↗

PubMed1977

Enhancement of antibody-dependent cell-mediated cytotoxicity of herpesvirus-infected cells by complement.

An investigation was made of the effects of complement on the levels of antibody-dependence cytotoxicity (ADCC) mediated by bovine leukocytes against herpesvirus-infected target cells. Neutrophil-mediated ADCC was considerably enhanced upon the addition of low levels of complement that alone failed to induce lysis of antibody-sensitized target cells. This enhancement was most apparent under suboptimum conditions such as at low effector-to-target cell ratios, low levels of sensitizing antiserum, and short-duration assays. Furthermore, cells and classes of immunoglobulin unable to induce ADCC could do so in the presence of complement. The action of complement is considered in terms of a more tenacious bond formed between effector and target cells. The implications of the results are discussed in terms of the part that complement might play in enhancing antiviral recovery processes.

Antibodies↗

PubMed1978

Potential for immunization against herpesvirus infections with plasma membrane vesicles.

Virus-free, membrane antigen (MA)-positive plasma membrane vesicles produced from herpesvirus saimiri-infected owl monkey cells were used as immunogens in cotton-top marmosets. Neutralizing antibodies as well as antibodies to MA and HVS-induced LA were induced following immunization of marmosets with these vesicles. Preliminary findings demonstrated that immunized marmosets were significantly less susceptible to tumour induction by HVS than control animals.

Animals↗